Childhood dietary patterns and ADHD?

The findings of the systematic review and meta-analysis published by Bianca Del-Ponte and colleagues [1] provide the blogging fodder today, and the suggestion that: "a diet high in refined sugar and saturated fat can increase the risk, whereas a healthy diet, characterized by high consumption of fruits and vegetables, would protect against ADHD [attention-deficit hyperactivity disorder] or hyperactivity."

The starting point: "The diet during childhood has been investigated as a factor potentially involved in the ADHD etiology." Yes it has, and Del-Ponte et al managed to find 14 studies looking at this issue published in the peer-reviewed literature. The data were boiled down and results obtained suggesting that "healthy dietary patterns were protective against ADHD (OR: 0.65; 95% CI: 044 – 0.97), while unhealthy dietary patterns were found as risk to ADHD (OR: 1.41; 95% CI: 1.15–1.74)."

The authors admit that the science upon which they made their observation is "weak" insofar as cause and effect not being proved. This is an important point (see here) that follows other research in this area too (see here and see here) together with an understanding that many different variables *might* influence the risk of something like ADHD as a diagnosis or in behaviour (see here and see here for examples).

Still, if there is even the remotest possibility that diet might be something to consider in respect of ADHD, adding it to the intervention arsenal that already exists (see here) can only be a good thing...

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[1] Del-Ponte B. et al. Dietary patterns and attention deficit/hyperactivity disorder (ADHD): A systematic review and meta-analysis. Journal of Affective Disorders. 2019; 252: 160-173.

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"Maternal diabetes, especially GDM, is probably a risk factor for ADHD"

It's coincidental that as I write this post about the findings reported by Lifeng Zhao and colleagues [1] talking about how "Maternal diabetes, especially GDM [gestational diabetes mellitus], is probably a risk factor for ADHD [attention-deficit hyperactivity disorder]" so the BBC news website highlights how screening for gestational diabetes here in Blighty is still a bit of a hit-and-miss affair (see here).

That news report mentions how about a quarter of those mums-to-be who are most at risk of developing pregnancy diabetes - "having a high BMI [body mass index] or being of South Asian or Black Caribbean ethnicity" - did not get screened at all. Left untreated, gestational or pregnancy diabetes can increase the risk of various adverse events including "a baby that grows larger than usual, leading to problems in labour; premature birth; pre-eclampsia and stillbirth."

The Zhao findings - a meta-analysis - continue a theme suggesting that exposure to maternal diabetes, including pregnancy diabetes, seems to increase the risk of various other developmental and behavioural diagnoses also being present in offspring. The primary source material of this blog - autism - has been talked about on various occasions as being one of those developmental/behavioural diagnoses (see here and see here). That ADHD is quite often mentioned in the diagnostic mix when it comes to autism (see here) is another point to make.

The basics of the Zhao paper: a search of the peer-reviewed science literature was undertaken revealing nine studies that fitted the inclusion criteria including "7,218,903 participants." The quality of most studies was ranked as high. The results were interesting in that researchers "did not find significant association between maternal diabetes and ADHD risk (OR: 1.20, 95% CI: 0.96–1.49)." This observation is slightly at odds with the quote titling this post, which Zhao et al put down to the "high heterogeneity" detected among the included studies and their subgroup analysis of case-control studies (n=3).

Also... when it came to looking at another type of study - a cohort study (n=6) - "the meta-analysis demonstrated that maternal diabetes increased the risk of ADHD in offspring by 40%." Further, and bearing in mind the description 'diabetes' covers quite a bit of diagnostic ground, authors zoomed in on one particular 'type of diabetes', that called gestational diabetes (GDM) and looked at any effect. This is where things got a little more interesting as their results, based on four studies, indicated that "GDM exposure increased the risk of ADHD for children by 164%" in Caucasian children. Ergo, although a little mixed, the existing research literature at the time of analysis indicated that maternal diabetes during pregnancy, particularly GDM, *might* have some important effect on risk of offspring ADHD.

I'm not going to say much more at this point in time in terms of potential mechanisms that *might* elevate the risk of ADHD in offspring exposed to pregnancy diabetes. It's likely to be pretty complicated. Given also that GDM appears more often than not alongside other conditions (see here), it's not going to be easy to tease apart what might be the more important issues. Is it inflammation? Is something to do with blood sugar or insulin? At the moment, we just don't know enough...

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[1] Zhao L. et al. The association of maternal diabetes with attention deficit and hyperactivity disorder in offspring: a meta-analysis. Neuropsychiatr Dis Treat. 2019;15:675–684.
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A few-foods diet for ADHD: a systematic review of meta-analyses of double-blind, placebo-controlled trials

"... the effect sizes of a few-foods diet are medium to large, justifying implementation of a diagnostic FFD [few-foods diet] in subgroups of children with ADHD [attention-deficit hyperactivity disorder], thus offering innovative treatment opportunities for ADHD."

So said the "Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials" published by Lidy Pelsser and colleagues [1] (open-access available here) looking at various dietary interventions that have been studied with ADHD in mind. Pelsser, I might add, is a name not completely unfamiliar to this area of investigation as per other research on elimination diets and ADHD (see here).

The few-foods diet mentioned in the opening sentence of this post, could include a few things but Pelsser et al make specific reference to it consisting of "lamb, chicken, potatoes, rice, banana, apple and brassica: foods chosen as they were unlikely to produce an adverse response." You'll perhaps note that there are a few food groups missing from that list of foods, not least the grains (including the gluten protein), dairy products (containing the casein protein) and those processed foods that we all like to enjoy.

The Pelsser paper is an interesting one insofar as their systematically reviewing meta-analyses that were already conducted on dietary intervention(s) for ADHD. Said meta-analyses included in their paper were only allowed in if they meta-analysed double-blind placebo-controlled trials (the gold-standard of clinical trial design). If one assumes that a meta-analysis - where data from different trials is analysed and condensed into a sort of position statement - sits at the top of the evidence-based science hierarchy, the Pelsser study design perhaps sits on top of the top!

Although the FFD receives some welcome scientific backing in the review paper, it was not the only dietary intervention looked at the Pelsser and colleagues. To quote: "six supplement meta-analyses—all investigating the effects of poly-unsaturated fatty acids (PUFA)... —and eight elimination meta-analyses, examining respectively the effects of sugar..., AFC [artificial food colour elimination]..., the Feingold diet..., and the FFD... on ADHD" were reported on. The other interventions did not - for various possible reasons - match up to the research success reported with regards to the current standing of the few-foods diet for ADHD. This included the story on fatty acids for ADHD which has been mentioned previously on this blog (see here for example).

I do not make recommendations on this blog when it comes to intervention and the like for anything. I will however, once again quote Pelsser et al based on their very thorough analysis of the peer-reviewed science in the area of dietary intervention for ADHD: "the effect sizes of a few-foods diet are medium to large, justifying implementation of a diagnostic FFD in subgroups of children with ADHD, thus offering innovative treatment opportunities for ADHD". Also: "FFD research should focus on the mechanism of food in children with ADHD." Their words not mine, and based on some rather credible evidence. I might also add that appropriate dietetic input is a must before anyone heads into the FFD willy-nilly and no, this is not about 'clean eating' or any related fad...

And just before you go, how about casting your eye over the observations made by Alejandra Ríos-Hernández and colleagues [2] and their raising the question of "whether low adherence to a Mediterranean diet might play a role in ADHD development"? Food for thought in the context of the Pelsser data, although perhaps minus the [pregnancy] licorice?

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[1] Pelsser LM. et al. Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD. PLoS One. 2017 Jan 25;12(1):e0169277.

[2] Ríos-Hernández A. et al. The Mediterranean Diet and ADHD in Children and Adolescents. Pediatrics. 2017. Jan 30.

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Pelsser LM, Frankena K, Toorman J, & Rodrigues Pereira R (2017). Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD. PloS one, 12 (1) PMID: 28121994

A prenatal 'unhealthy' diet and offspring ADHD?

'Scientists study link between unhealthy pregnancy diet and ADHD' went one media headline covering the paper by Jolien Rijlaarsdam and colleagues [1].

The name of the research game was again to draw on data derived from ALSPAC (Avon Longitudinal Study of Parents and Children) (yes, again) to look-see "the degree to which prenatal high-fat and -sugar diet might relate to ADHD [attention-deficit hyperactivity disorder] symptoms via IGF2 DNA methylation for early-onset persistent (EOP) versus low CP [conduct problems] youth." In other words: "Experts examine how a diet high in fat and sugar could alter baby’s DNA in a way that might cause behavioural problems."

To do this meant looking at around 80 youth presenting with early-onset conduct problems compared with around 80 youths who didn't have the same magnitude of issues. Data on maternal nutrition captured for the two groups (ALSPAC did a lot of data collecting!) was cross-referenced with group status and also epigenetic - methylation - status of the insulin-like growth factor 2 gene (IGF2). IGF2 is a gene that seems to be pretty active during the nine months that made us but less so as we enter the big, wide world. As the name suggests it seems to have a 'growth' role which is probably why issues with this gene have also been associated with the development of a number of cancers.

Results: "Prenatal ‘unhealthy diet’ was positively associated with IGF2 methylation at birth for both the EOP and low CP youth." Minus any 'blame', such results suggest that maternal diet might be important for the developing child. I know this is it not exactly a shock, but in these days of more and more research and clinical focus on the special time called pregnancy, the idea that particular epigenetic changes might come from a chosen diet is a potentially important one.

Further: "For EOP only: (a) higher IGF2 methylation predicted ADHD symptoms; and (b) prenatal ‘unhealthy diet’ was associated with higher ADHD symptoms indirectly via higher IGF2 methylation." The higher IGF2 methylation - higher ADHD symptoms is an interesting association. Methylation - the addition of a methyl group - is normally taken to mean gene silencing suggesting that a malfunction of the the IGF2 gene and/or lower levels of its protein product might have some important implications. At this point I might add that whilst there is a bit of a research gap when it comes to IGF2 and behaviour specifically linked to ADHD, there is some interesting animal research looking at mice engineered to show low levels of the protein product in terms of behaviours such as anxiety [2] alongside "a role for the placenta in long-term programming of emotional behaviour." Cutting edge stuff to be sure.

"At present, this is not a study that would change my clinical practice, but if intervention studies resulting from this work show nutritional support in pregnancy can have an effect then we should take any opportunity we can to help." That was one comment from a physician discussing the results of the Rijlaarsdam study that I would agree with. The fact that the study focuses on just one gene in amongst the thousands potentially linked to conduct problems and ADHD is something to bear in mind.

Set however within the context that food can seemingly also affect behaviour and psychiatry as well as physiology (see here for example) I'd like to think that more studies on nutrition during pregnancy would be forthcoming and quickly on this important topic.

To close, thanks to Gene for the laughter...

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[1] Rijlaarsdam J. et al. Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems. J Child Psychol Psychiatry. 2016 Aug 18.

[2] Mikaelsson MA. et al. Placental programming of anxiety in adulthood revealed by Igf2-null models. Nat Commun. 2013;4:2311.

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Rijlaarsdam J, Cecil CA, Walton E, Mesirow MS, Relton CL, Gaunt TR, McArdle W, & Barker ED (2016). Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems. Journal of child psychology and psychiatry, and allied disciplines PMID: 27535767